In most cases, human contact with chemical substances can be characterized as being of the low-level exposure type. To predict the likelihood that such exposure may adversely impact an individual, simulative studies are performed in animals exposing them to such chemicals in nearly the same manner as humans are exposed, that is, in the diet, by inhalation, or by dermal application.
The validity of the use of data obtained from experiments with animals in providing some indication of the existence and severity of the potential hazards which humans are subjected to in certain situations depends upon correlations grounded in actual experience with those situations. The use of rodents in the estimation of the relative carcinogenic activity of various materials on human skin is broadly accepted. The general similarity of response of the skin of rodents and humans to certain known carcinogenic materials, including shale oils, spindle oils and the like, is well documented. Exemplary studies are found in: Leitch, A., "Paraffin Cancer and Its Experimental Production," British Medical Journal, 2:1104-6, 1922; Scott, A., "On the Occupation Cancer of the Paraffin and Oil Workers in the Scottish Shale Oil Industry," British Medical Journal, 2:1108-9, 1940; Twort, C. C. and Twort, J. M., "The Relative Potency of Carcinogenic Tars and Oils," Journal of Hygiene, 29:373-79, 1930; and, Horton, A. W. and Denman, D. T., "Carcinogenesis of the Skin. A Reexamination of Methods for the Quantitative Measurement of the Potencies of Complex Materials," Cancer Research, 15:701-09, 1955.
During the past seventy years, methods for evaluating systemic hazards from skin contact have been used on a large scale, and it has now become common practice to determine the toxicity of a new material by dermal application. The National Research Council has published a summary of methods for the evaluation of skin irritancy, the most common of which employ the use of small animals, such as guinea pigs, rabbits, rats and mice. See Committee on Toxicology, "Principles and Procedures for Evaluating the Toxicity of Household Substances," Pub. No. 1138, National Academy of Sciences, National Research Council, Washington, D.C., 1964.
Generally, when determining acute dermal toxicity, chemical substances are applied to the clipped skin of the animal in varying quantities and held in place for 24 hours by a sleeve of occlusive plastic sheeting or a rubber dam. Observations are made for at least two weeks. Such tests allow an estimate of the hazard of serious systemic effects by dermal contact, and they may give an idea of the rapidity of absorption. Generally they do not provide a quantitative measure of the percentage of the applied dose that has penetrated the skin. Some substances may be absorbed into the skin but not penetrate it. Quantitative data can be obtained in a variety of ways such as by tracer substances or measuring their concentration in blood or excretion in urine. Evaluations in these and other related tests often include clinical observations, weight gain, skin irritation, and blood cell and serum chemistry evaluations. At the end of a study, gross and microscopic examinations and sperm evaluations may be performed.
While occlusive sheeting and the like find utility in various chemical absorption studies, such as the aforementioned acute dermal toxicity study, other dermal assessments require the use of non-occlusive coverings for the treated area. For example, when seeking to assess the impact of low-level human chemical exposure, permitting the skin of the test animal to breathe in the usual manner enhances the simulative value of the test. While leaving the treated area of the test animal uncovered would be desirable from the standpoint of human exposure simulation, doing so often allows the animal to remove the substance in any of a variety of ways, thus impairing test integrity. For example, during grooming, the animal could potentially ingest the material and, thus, destroy the ability to assess the impact of the material through dermal absorption, alone. To aid in the small-dose study of materials having good percutaneous absorption characteristics, small, disk-like cells, such as the 1.25 centimeters diameter teflon cell available from Crown Glass Company, of Somerville, N.J., have been developed. Such cells are generally provided with an adhesive material applied to its perimeter for affixing the cell to the test animal. While these non-occlusive cells function adequately when used to study the types of materials for which they were designed to accommodate, they are inadequate in the study of materials of lower dermal penetration, such as those encountered in the study of contaminated soils.
Concern regarding dermal exposure to soils contaminated with potentially toxic materials such as dioxins, pesticides, heavy metals, polynuclear aromatics (PNA) and petroleum products containing PNA, has prompted the government and private sector to examine and formulate dermal risk assessment methodologies for contaminated soils. In the absence of experimentally determined percutaneous absorption values, many risk assessment schemes substitute available animal toxicology data on the pure contaminant, estimate dermal penetration of pure contaminant based on physicochemical models or, in the extreme, assume 100% bioavailability of the contaminant for soil (U.S. EPA 1986). Risk assessment based on these approaches is likely to result in an overestimate of dermal bioavailability of contaminants from soil, particularly for the water insoluble lipophilic compounds found in petroleum products. Therefore, toxicology data obtained using actual samples of contaminated soils are needed to provide proper risk assessment of these materials.
As mentioned, contaminated soils generally possess low dermal penetration characteristics. As such, they must be applied to a larger portion of the dorsal area of the animal to properly assess the risk of exposure to such a material. While many pure substances may be adequately tested by applying them to as little as one square centimeter of the dorsal area of an animal, to test substances of poor dermal penetration, such as contaminated soils, areas in excess of five square centimeters must often be treated. Because of the necessity to treat a relatively large area of the animal's dorsal region, the presently known non-occlusive cells are clearly inadequate. Merely fabricating a larger flat, disk-like, non-occlusive cell would not be satisfactory since, as the animal moves about, its skin-layer would move to an extent sufficient to cause contact with such a larger disk-like cell. This contact of the treated dorsal area with the surface of the cell would substantially impair the integrity of the evaluation. Also, there exists a practical difficulty when attempting to attach a disk-like cell to the dorsal area of an animal, particularly when using a flat cell having a cross-sectional area of at least 5 cm.sup.2. This is due to the fact that proper adhesion of such a cell to the dorsal skin cannot be achieved over the entire contact area.
Therefore, what is needed is a cell capable of protecting an area of skin large enough to permit the testing of materials having lower dermal penetration characteristics without permitting the contact of treated skin with the cell.